Aroop Sircar - Incorporating biochemical information and backbone flexibility in RosettaDock for CAPRI rounds 6-12

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      Publication Details (including relevant citation   information):

      Sid Chaudhury, Aroop Sircar, Arvind Sivasubramanian, Monica   Berrondo, Jeffrey J. Gray

      Proteins 69(4), 793-800, September 25, 2007.


      In CAPRI rounds 6–12, RosettaDock successfully predicted 2 of 5   unbound–unbound targets to medium accuracy. Improvement over the   previous method was achieved with computational mutagenesis to   select decoys that match the energetics of experimentally   determined hot spots. In the case of Target 21, Orc1/Sir1, this   resulted in a successful docking prediction where RosettaDock   alone or with simple site constraints failed. Experimental   information also helped limit the interacting region of TolB/Pal,   producing a successful prediction of Target 26. In addition, we   docked multiple loop conformations for Target 20, and we   developed a novel flexible docking algorithm to simultaneously   optimize backbone conformation and rigid-body orientation to   generate a wide diversity of conformations for Target 24.   Continued challenges included docking of homology targets that   differ substantially from their template (sequence identity   <50%) and accounting for large conformational changes upon   binding. Despite a larger number of unbound–unbound and homology   model binding targets, Rounds 6–12 reinforced that RosettaDock is   a powerful algorithm for predicting bound complex structures,   especially when combined with experimental data

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